Modular Design

Electromechanical wave imaging (EWI) has recently been introduced as a noninvasive, ultrasound-based imaging modality, which could map the electrical activation of the heart in various echocardiographic planes in mice, dogs, and humans in vivo. By acquiring radio-frequency (RF) frames at very high frame rates (390-520 Hz), the onset of small, localized, transient deformations resulting from the electrical activation of the heart, i.e., generating the electromechanical wave (EMW), can be mapped. The correlation between the EMW and the electrical activation speed and pacing scheme has previously been reported. In this study, we pursue the development of EWI using both displacements and strains and analysis of the EMW properties in dogs in vivo for early detection of ischemia. EWI was performed in normal and ischemic open-chest dogs during sinus rhythm. Ischemia of increasing severity was obtained by gradually obstructing the left-anterior descending (LAD) coronary artery flow. We also introduce the novel method of motion-matching that achieves the reconstruction of the full EWI cine-loop at very high frame rates even when the ECG may be irregular or unavailable. Incremental displacements were previously used by our group to map the EMW. This paper focuses on the associated incremental strains, which facilitate the interpretation of the EMW by relating it directly to contraction. Moreover, we define the onset of the EMW as the time, at which the incremental strains change sign after the onset of the QRS complex of the ECG. Based on this definition, isochronal representations of the EMW were generated using a semi-automated method. The isochronal representation of the EMW during sinus rhythm was reproducible and shown similar to electrical activation maps previously reported in the literature. After segmentation using a contour-tracking method, the two- and four-chamber views were imaged and displayed in bi-plane views, allowing a 3-D interpretation of th- EMW. EWI was shown to be sensitive to the presence of intermediate ischemia. EWI localized the ischemic region when the LAD flow was obstructed at 60% and beyond and was capable of mapping the increase of the ischemic region size as the LAD occlusion level increased. In conclusion, the activation maps and wave patterns obtained with EWI were similar to the electrical equivalents previously reported in the literature. Moreover, EWI was found to be sensitive enough to detect and map intermediate ischemia. Those results indicate that EWI could be used to assess the conduction properties of the myocardium, and detect its ischemic onset and disease progression entirely noninvasively.

Concern about the performance of wires wires in scaled technologies has led to research exploring other communication methods. This paper examines wire and gate delays as technologies migrate from 0.18-μm to 0.035-μm feature sizes to better understand the magnitude of the the wiring problem. Wires that shorten in length as technologies scale have delays that either track gate delays or grow slowly relative to gate delays. This result is good news since these “local” wires dominate chip wiring. Despite this scaling of local wire performance, computer-aided design (CAD) tools must still become move sophisticated in dealing with these wires. Under scaling, the total number of wires grows exponentially, so CAD tools will need to handle an ever-growing percentage of all the wires in order to keep designer workloads constant. Global wires present a more serious problem to designers. These are wires that do not scale in length since they communicate signals across the chip. The delay of these wives will remain constant if repeaters are used meaning that relative to gate delays, their delays scale upwards. These increased delays for global communication will drive architectures toward modular designs with explicit global latency mechanisms

By analyzing the human antibody repertoire in terms of structure, amino acid sequence diversity and germline usage, we found that seven V H and seven V L (four Vk and three Vl) germline families cover more than 95 % of the human antibody diversity used. A consensus sequence was derived for each family and optimized for expression in Escherichia coli. In order to make all six complementarity determining regions (CDRs) accessible for diversi®cation, the synthetic genes were designed to be modular and mutually compatible by introducing unique restriction endonuclease sites¯anking the CDRs. Molecular modeling veri®ed that all canonical classes were present. We could show that all master genes are expressed as soluble proteins in the periplasm of E. coli. A ®rst set of antibody phage display libraries totalling 2 Â 10 9 members was created after cloning the genes in all 49 combinations into a phagemid vector, itself devoid of the restriction sites in question. Diversity was created by replacing the V H and V L CDR3 regions of the master genes by CDR3 library cassettes, generated from mixed trinucleotides and biased towards natural human antibody CDR3 sequences. The sequencing of 257 members of the unselected libraries indicated that the frequency of correct and thus potentially functional sequences was 61 %. Selection experiments against many antigens yielded a diverse set of binders with high af®nities. Due to the modular design of all master genes, either single binders or even pools of binders can now be rapidly optimized without knowledge of the particular sequence, using pre-built CDR cassette libraries. The small number of 49 master genes will allow future improvements to be incorporated quickly, and the separation of the frameworks may help in analyzing why nature has evolved these distinct subfamilies of antibody germline genes.

Endocytosis depends on an extensive network of interacting proteins that execute a series of distinct subprocesses. Previously, we used live-cell imaging of six budding-yeast proteins to define a pathway for association of receptors, adaptors, and actin during endocytic internalization. Here, we analyzed the effects of 61 deletion mutants on the dynamics of this pathway, revealing functions for 15 proteins, and we analyzed the dynamics of 8 of these proteins. Our studies provide evidence for four protein modules that cooperate to drive coat formation, membrane invagination, actin-meshwork assembly, and vesicle scission during clathrin/actin-mediated endocytosis. We found that clathrin facilitates the initiation of endocytic-site assembly but is not needed for membrane invagination or vesicle formation. Finally, we present evidence that the actin-meshwork assembly that drives membrane invagination is nucleated proximally to the plasma membrane, opposite to the orientation observed for previously studied actin-assembly-driven motility processes.

This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009.
The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480–1250 GHz with SIS mixers and the 1410–1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1.
After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations.

Wnt signaling plays an important role in both oncogenesis and development. Activation of the Wnt pathway results in stabilization of the transcriptional coactivator b-catenin. Recent studies have demonstrated that axin, which coordinates b-catenin degradation, is itself degraded. Although the key molecules required for transducing a Wnt signal have been identified, a quantitative understanding of this pathway has been lacking. We have developed a mathematical model for the canonical Wnt pathway that describes the interactions among the core components: Wnt, Frizzled, Dishevelled, GSK3b, APC, axin, b-catenin, and TCF. Using a system of differential equations, the model incorporates the kinetics of protein-protein interactions, protein synthesis/degradation, and phosphorylation/ dephosphorylation. We initially defined a reference state of kinetic, thermodynamic, and flux data from experiments using Xenopus extracts. Predictions based on the analysis of the reference state were used iteratively to develop a more refined model from which we analyzed the effects of prolonged and transient Wnt stimulation on b-catenin and axin turnover. We predict several unusual features of the Wnt pathway, some of which we tested experimentally. An insight from our model, which we confirmed experimentally, is that the two scaffold proteins axin and APC promote the formation of degradation complexes in very different ways. We can also explain the importance of axin degradation in amplifying and sharpening the Wnt signal, and we show that the dependence of axin degradation on APC is an essential part of an unappreciated regulatory loop that prevents the accumulation of b-catenin at decreased APC concentrations. By applying control analysis to our mathematical model, we demonstrate the modular design, sensitivity, and robustness of the Wnt pathway and derive an explicit expression for tumor suppression and oncogenicity.

Developing product architectures is a key phase in design and development processes. It encompasses the transformation of product function to alternative product layouts. In this paper, we describe a new approach for identifying modules for product architectures. We begin by reviewing the terminology and motivation for modular products. The new concepts of a functional basis and time ordered function chains are used to formally derive functional models of products. Then, three heuristic methods for identifying modules from functional models are presented. Using the formal functional decomposition and heuristic methods, modular design can be executed earlier in the product development process, as illustrated by the example of a consumer power-tool product and a larger, complex maintenance device. A database of 70 consumer products is used to verify and confirm the overall modular design approach.

We present an update to STIR, an Open Source object-oriented library in C++ for 3D PET reconstruction. This library has been designed so that it can be used for many algorithms and scanner geometries, while being portable to various computing platforms. This second release enhances its flexibility and modular design, but also adds extra capabilities such as list mode reconstruction, more data formats etc.

Nervous systems are information processing networks that evolved by natural selection, whereas very large scale integrated (VLSI) computer circuits have evolved by commercially driven technology development. Here we follow historic intuition that all physical information processing systems will share key organizational properties, such as modularity, that generally confer adaptivity of function. It has long been observed that modular VLSI circuits demonstrate an isometric scaling relationship between the number of processing elements and the number of connections, known as Rent's rule, which is related to the dimensionality of the circuit's interconnect topology and its logical capacity. We show that human brain structural networks, and the nervous system of the nematode C. elegans, also obey Rent's rule, and exhibit some degree of hierarchical modularity. We further show that the estimated Rent exponent of human brain networks, derived from MRI data, can explain the allometric scaling relations between gray and white matter volumes across a wide range of mammalian species, again suggesting that these principles of nervous system design are highly conserved. For each of these fractal modular networks, the dimensionality of the interconnect topology was greater than the 2 or 3 Euclidean dimensions of the space in which it was embedded. This relatively high complexity entailed extra cost in physical wiring: although all networks were economically or cost-efficiently wired they did not strictly minimize wiring costs. Artificial and biological information processing systems both may evolve to optimize a trade-off between physical cost and topological complexity, resulting in the emergence of homologous principles of economical, fractal and modular design across many different kinds of nervous and computational networks.

This paper proposes a cross-layer optimization framework that provides efficient allocation of wireless network resources across multiple types of applications to maximize network capacity and user satisfaction. We define a novel optimization scheme based on the Mean Opinion Score (MOS) as the unifying metric. Our experiments, applied to scenarios where users simultaneously run three types of applications, such as realtime voice, video conferencing and file download, confirm that MOS-based optimization leads to significant improvement in terms of user perceived quality when compared to throughput-based optimization.

We present a program visualization tool called Jeliot 3 that is designed to aid novice students to learn procedural and object oriented programming. The key feature of Jeliot is the fully or semi-automatic visualization of the data and control flows. The development process of Jeliot has been research-oriented, meaning that all the different versions have had their own research agenda rising from the design of the previous version and their empirical evaluations. In this process, the user interface and visualization has evolved to better suit the targeted audience, which in the case of Jeliot 3, is novice programmers. In this paper we explain the model for the system and introduce the features of the user interface and visualization engine. Moreover, we have developed an intermediate language that is used to decouple the interpretation of the program from its visualization. This has led to a modular design that permits both internal and external extensibility.

We present first results of our search for high-redshift galaxies in deep CCD mosaic images. As a pilot study for a larger survey, very deep images of the Chandra Deep Field South (CDFS), taken with WFI@MPG/ESO2.2m, are used to select large samples of 1070 U-band and 565 B-band dropouts with the Lyman-break method. The data of these Lyman-break galaxies are made public as an electronic table. These objects are good candidates for galaxies at z ∼ 3 and z ∼ 4 which is supported by their photometric redshifts. The distributions of apparent magnitudes and the clustering properties of the two populations are analysed, and they show good agreement to earlier studies. We see no evolution in the comoving clustering scale length from z ∼ 3 to z ∼ 4. The techniques presented here will be applied to a much larger sample of U-dropouts from the whole survey in near future.

M odularity has been heralded as an organizational and technical architecture that enhances incremental and modular innovation. Less attention has been paid to the possible implications of modular architectures for imitation. To understand the implications of modular designs for competitive advantage, one must consider the dual impact of modularity on innovation and imitation jointly. In an attempt to do so, we set up three alternative structures that vary in the extent of modularity and hence in the extent of design complexity: nonmodular, modular, and nearly modular designs. In each structure, we examine the trade-offs between innovation benefits and imitation deterrence. The results of our computational experiments indicate that modularization enables performance gains through innovation but, at the same time, sets the stage for those gains to be eroded through imitation. In contrast, performance differences between the leaders and imitators persist in the nearly modular and the nonmodular structures. Overall, we find that design complexity poses a significant trade-off between innovation benefits (i.e., generating superior strategies that create performance differences) and imitation deterrence (i.e., preserving the performance differences). We also examine the robustness of our results to variations in imitation accuracy. In addition to documenting the overall robustness of our principal finding, the ancillary analyses provide a more nuanced rendering of the relationship between the architecture of complexity and imitation efforts.

We study the dynamics of modularization in a minimal substrate. A module is a functional unit relatively separable from its surrounding structure. Although it is known that modularity is useful both for robustness and for evolvability , there is no quantitative model describing how such modularity might originally emerge. Here we suggest, using simple computer simulations, that modularity arises spontaneously in evolutionary systems in response to variation, and that the amount of modular separation is logarithmically proportional to the rate of variation. Consequently, we predict that modular architectures would appear in correlation with high environmental change rates. Because this quantitative model does not require any special substrate to occur, it may also shed light on the origin of modular variation in nature. This observed relationship also indicates that modular design is a generic phenomenon that might be applicable to other fields, such as engineering: Engineering design methods based on evolutionary simulation would benefit from evolving to variable, rather than stationary, fitness criteria, as a weak and problem-independent method for inducing modularity.

Growth factors have become an important component for tissue engineering and regenerative medicine. Insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-b 1 ) in particular have great significance in cartilage tissue engineering. Here, we describe sequential release of IGF-I and TGF-b 1 from modular designed poly(L,D-lactic-co-glycolic acid) (PLGA) scaffolds. Growth factors were encapsulated in PLGA microspheres using spontaneous emulsion, and in vitro release kinetics was characterized by ELISA. Incorporating BSA in the IGF-I formulations decreased the initial burst from 80% to 20%, while using uncapped PLGA rather than capped decreased the initial burst of TGF-b 1 from 60% to 0% upon hydration. The bioactivity of released IGF-I and TGF-b 1 was determined using MCF-7 proliferation assay and HT-2 inhibition assay, respectively. Both growth factors were released for up to 70 days in bioactive form. Scaffolds were fabricated by fusing bioactive IGF-I and TGF-b 1 microspheres with dichloromethane vapor. Three scaffolds with tailored release kinetics were fabricated: IGF-I and TGF-b 1 released continuously, TGF-b 1 with IGF-I released sequentially after 10 days, and IGF-I with TGF-b 1 released sequentially after 7 days. Scaffold swelling and degradation were characterized, indicating a peak swelling ratio of 4 after 7 days of incubation and showing 50% mass loss after 28 days, both consistent with scaffold release kinetics. The ability of these scaffolds to release IGF-I and TGF-b 1 sequentially makes them very useful for cartilage tissue engineering applications.

Identifying new intrusions and developing effective signatures that detect them is essential for protecting computer networks. We present Nemean, a system for automatic generation of intrusion signatures from honeynet packet traces. Our architecture is distinguished by its emphasis on a modular design framework that encourages independent development and modification of system components and protocol semantics awareness which allows for construction of signatures that greatly reduce false alarms. The building blocks of our architecture include transport and service normalization, intrusion profile clustering and automata learning that generates connection and session aware signatures. We demonstrate the potential of Nemean's semantics-aware, resilient signatures through a prototype implementation. We use two datasets to evaluate the system: (i) a production dataset for false-alarm evaluation and (ii) a honeynet dataset for measuring detection rates. Signatures generated by Nemean for NetBIOS exploits had a 0% false-positive rate and a 0.04% false-negative rate.

w . The first version of the Human Combinatorial Antibody Library HuCAL is a single-chain Fv-based phage display Ž w . 9 library HuCAL -scFv with 2 = 10 members optimised for high-throughput generation and targeted engineering of human antibodies. 61% of the library genes code for functional scFv as judged by sequencing. We show here that since HuCAL w -scFv antibodies are expressed in high levels in Escherichia coli, automated panning and screening in miniaturised Ž .

In this paper the design problems encountered when designing heterogeneous systems are studied and solutions to these problems are proposed. It will be shown why a single heterogeneous specification method ranging from concept to architecture is required and why it should cover issues as modularity, design for reuse, reuse of designs and reuse of design environments. A heterogeneous system design environment based on co-specification, co-simulation and cosynthesis is proposed and its application is illustrated by means of a spread spectrum based pager system.

Vectors have been developed for inducible gene expression in Lactobacillus sakei and Lactobacillus plantarum in which expression of the gene of interest is driven by strong, regulated promoters from bacteriocin operons found in L. sakei strains. The activity of these promoters is controlled via a two-component signal transduction system, which responds to an externally added peptide pheromone. The vectors have a modular design, permitting easy exchange of all essential elements: the inducible promoter, the cognate regulatory system, the gene of interest, the antibiotic resistance marker and the replicon. Various variants of these so-called 'pSIP' vectors were constructed and tested, differing in terms of the bacteriocin regulon from which the regulatory elements were derived (sakacin A or sakacin P), the regulated promoter selected from these regulons, and the replicon (derived from p256 or pSH71). Using b-glucuronidase (GusA) and aminopeptidase N (PepN) as reporters, it was shown that the best vectors permitted inducible, pheromone-dose-dependent gene expression at very high levels, while displaying moderate basal activities when not induced. The most effective set-up was obtained using a vector containing the pSH71 replicon, the orfX promoter from the sakacin P regulon, and the cognate regulatory genes, in a L. sakei host. GusA levels obtained with this set-up were approximately ten times higher than the levels obtained with prototype pSIP versions, whereas PepN levels amounted to almost 50 % of total cellular protein.

Background: Instructions to fabricate mineralized structures with distinct nanoscale architectures, such as seashells and coral and vertebrate skeletons, are encoded in the genomes of a wide variety of animals. In mollusks, the mantle is responsible for the extracellular production of the shell, directing the ordered biomineralization of CaCO 3 and the deposition of architectural and color patterns. The evolutionary origins of the ability to synthesize calcified structures across various metazoan taxa remain obscure, with only a small number of protein families identified from molluskan shells. The recent sequencing of a wide range of metazoan genomes coupled with the analysis of gene expression in non-model animals has allowed us to investigate the evolution and process of biomineralization in gastropod mollusks.

We have developed a General Ecosystem Model (GEM) that is designed to simulate a variety of ecosystem types using a fixed model structure. Driven largely by hydrologic algorithms for upland, wetland and shallow-water habitats, the model captures the response of macrophyte and algal communities to simulated levels of nutrients, water, and environmental inputs. It explicitly incorporates ecological processes that determine water levels, plant production, nutrient cycling associated with organic matter decomposition, consumer dynamics, and fire. While the model may be used to simulate ecosystem dynamics for a single homogenous habitat, our primary objective is to replicate it as a "unit" model in heterogeneous, grid-based dynamic spatial models using different parameter sets for each habitat. Thus, we constrained the process (i.e., computational) complexity, yet targeted a level of disaggregation that would effectively capture the feedbacks among important ecosystem processes. A basic version was used to simulate the response of sedge and hardwood communities to varying hydrologic regimes and associated water quality. Sensitivity analyses provided examples of the model dynamics, showing the varying response of macrophyte production to different nutrient requirements, with subsequent changes in the sediment water nutrient concentrations and total water head. Changes in the macrophyte canopy structure resulted in differences in transpiration, and thus the total water levels and macrophyte production. The GEM's modular design facilitates understanding the model structure and objectives, inviting variants of the basic version for other research goals. Importantly, we hope that the generic nature of the model will help alleviate the "reinventing-the-wheel" syndrome of model development, and we are implementing it in a variety of systems to help understand their basic dynamics.

P roduct architecture and organizational communication play significant roles in complex product development efforts. By using networks to characterize both product structure and communication patterns, we examine the impact of mismatches between these on new product development (NPD) performance. Specifically, we study the vehicle development process of a major auto company and use vehicle quality (warranty repairs) as our NPD performance metric. Our empirical results indicate that centrality in a product architecture network is related to quality according to an inverted-U relationship, which suggests that vehicle subsystems of intermediate complexity exhibit abnormally high levels of quality problems. To identify specific subsystems in danger of excessive quality problems, we characterize mismatches between product architecture and organizational structure by defining a new metric, called coordination deficit, and show that it is positively associated with quality problems. These results deepen our understanding of the impact of organizational structure and product architecture on the NPD process and provide tools with which managers can diagnose and improve their NPD systems.

In this paper, related product functions are determined for a group of approximately 70 consumer products. Using customer need data, a new matrix approach is introduced to identify these relationships. Techniques are then created for determining product similarity. These techniques are clarified and validated through three case studies, including beverage brewers and material-removal products. The results of these case studies are argued to have significant impact on design-by-analogy procedures, benchmarking methods, mass customization strategies and modular design. The paper concludes with a discussion of applications and related procedures for product development. 1 From here forward, the word 'function' will be used interchangeably to mean overall product function and sub-function.

Tethered membranes have been proven during recent years to be a powerful and flexible biomimetic platform. We reported in a previous article on the design of a new architecture based on the self-assembly of a thiolipid on ultrasmooth gold substrates, which shows extremely good electrical sealing properties as well as functionality of a bilayer membrane. Here, we describe the synthesis of lipids for a more modular design and the adaptation of the linker part to silane chemistry. We were able to form a functional tethered bilayer lipid membrane with good electrical sealing properties covering a silicon oxide surface. We demonstrate the functional incorporation of the ion carrier valinomycin and of the ion channel gramicidin.

A strawberry fruit cDNA showing sequence similarity to higher-plant pectate lyase genes has been isolated by differential screening of a strawberry fruit cDNA subtractive library. The cDNA contains a 396 amino acids open reading frame corresponding to a 44.8 kDa protein. The transcript is predominantly expressed in ripe fruits and was not detected at high levels in any other plant tissues. The removal of the achenes from unripe green fruits induced the expression of this putative pectate lyase gene. In common with other ripening related genes in strawberry, this induction was partially inhibited by treatment of de-achened fruit with the auxin NAA. Southern blot analysis of genomic DNA indicates that in strawberry there is more than one putative pectate lyase gene. We propose that the ripe fruit expression of this strawberry gene with similarity to pectate lyases could be related to cell wall pectin degradation contributing to strawberry fruit softening.

Background: Genome assemblers have grown very large and complex in response to the need for algorithms to handle the challenges of large whole-genome sequencing projects. Many of the most common uses of assemblers, however, are best served by a simpler type of assembler that requires fewer software components, uses less memory, and is far easier to install and run.

We have been developing an overlay construction toolkit called Overlay Weaver as the groundwork for future research on algorithms. Algorithm designers can implement structured overlay algorithms in just hundreds of lines of code with the toolkit and improve these rapidly by iterative testing them on a single computer. The toolkit enables designers to make fair and large-scale comparisons between of new and existing algorithms, since the implemented algorithms are pluggable and the emulator provided by the toolkit can host thousands of virtual nodes. Furthermore, the implemented algorithms can work on a real network in addition to the emulator. The toolkit enables algorithms developed through research to be used in applications directly. We decomposed the routing layer of software which constructs structured overlay into a routing process and a routing algorithm. In this paper, we propose a programming interface between them. Decomposition enables an algorithm to be implemented in just hundreds of lines of code. The routing process also became pluggable by decomposition and the toolkit can provide both iterative and recursive routing.

A CMOS metal-electrode-based micro system for bidirectional communication (stimulation and recording) with neuronal cells in vitro is presented. The chip overcomes the interconnect challenge that limits today's bidirectional microelectrode arrays. The microsystem has been fabricated in an industrial CMOS technology with several post-CMOS processing steps to realize 128 biocompatible electrodes and to ensure chip stability in physiological saline. The system comprises all necessary control circuitry and on-chip A/D and D/A conversion. A modular design has been implemented, where individual stimulation-and signal-conditioning circuitry units are associated with each electrode. Stimulation signals with a resolution of 8 bits can be sent to any subset of electrodes at a rate of 60 kHz, while all electrodes of the chip are continuously sampled at a rate of 20 kHz. The circuitry at each electrode can be individually reset to its operating point in order to suppress artifacts evoked by the stimulation pulses. Biological measurements from cultured neuronal networks originating from dissociated cortical tissue of fertilized chicken eggs with amplitudes of up to 500 V pp are presented.

Biomolecular networks have to perform their functions robustly. A robust function may have preferences in the topological structures of the underlying network. We carried out an exhaustive computational analysis on network topologies in relation to a patterning function in Drosophila embryogenesis. We found that while the vast majority of topologies can either not perform the required function or only do so very fragilely, a small fraction of topologies emerges as particularly robust for the function. The topology adopted by Drosophila, that of the segment polarity network, is a top ranking one among all topologies with no direct autoregulation. Furthermore, we found that all robust topologies are modular-each being a combination of three kinds of modules. These modules can be traced back to three sub-functions of the patterning function and their combinations provide a combinatorial variability for the robust topologies. Our results suggest that the requirement of functional robustness drastically reduces the choices of viable topology to a limited set of modular combinations among which nature optimizes its choice under evolutionary and other biological constraints.

The Biopsychology-Toolbox is a free, open-source Matlab-toolbox for the control of behavioral experiments. The major aim of the project was to provide a set of basic tools that allow programming novices to control basic hardware used for behavioral experimentation without limiting the power and flexibility of the underlying programming language. The modular design of the toolbox allows portation of parts as well as entire paradigms between different types of hardware. In addition to the toolbox, this project offers a platform for the exchange of functions, hardware solutions and complete behavioral paradigms.

T his paper addresses the strategic impact of modular design on the optimal length and price of a differentiated product line. We represent consumer demand with a Bayesian logit model. We also break operations costs into product design and production components. Our analysis shows that reducing product development costs via modular design always makes it attractive to offer greater product variety. However, reducing production costs can sometimes motivate a reduction in variety for a risk-averse producer in a multiple-segment market. We also characterize the impacts of degree of modularity and production cost on price markup and market share. Finally, we show that the optimal product line length is monotonic in risk attitude and the monotonic weak majorization, partial order on product assortment.

A pilot-scale system for the intensive land-based culture of abalone was established using an integrated design aimed at eliminating the dependence on external food sources, whilst reducing water requirements and nutrient discharge levels. The system was the first and simplest trial in a series of progressive complexity of the concept of integrated culture of seaweed, abalone, fish and clams in modular and intensive land-based facilities. Relative sizes of the modules, their stocking densities and the rate of nutrient supply were determined based on earlier results to be optimal. Effluents from two abalone (Haliotis tuberculata) culture tanks drained into macroalgae (Ul6a lactuca or Gracilaria conferta) culture and biofilter tanks, where nitrogenous waste products contributed to the nutrition of the algae; net algal production from each algal tank was harvested and used to provide a mixed diet for the abalone. Excess algal yield was used elsewhere. The system was monitored to assess productivity and nitrogen partitioning over a year, while improvements were made based on the accumulating results. Total annual N-budgets were combined with mean production figures to determine a suitable ratio of abalone biomass to algal culture vessel productivity, towards commercial application of the concept. The abalone grew on average 0.26% and 0.25% body weight/d in the two culture tanks; reduced growth and increased food conversion ratios (food eaten/biomass gain; w/w) were associated with high summer water temperatures (max. 26.9°C). U. lactuca showed reliable growth and filtration performance (mean production of 230 g fresh weight/m 2 /d, removing on average 58% of nitrogen supplied). Conversely, G. conferta growth was highly erratic and was deemed unsuitable for the current application. A. Neori et al. / Aquacultural Engineering 17 (1998) 215-239 It is estimated that 1 kg of abalone biomass would require food supplied by 0.3 m 2 of U. lactuca culture, reducing N inputs required by 20% and N in effluent by 34% when compared to the two organisms grown in monoculture.

This paper presents four optimization models to demonstrate that the optimization of software reliability within the available resources can be accomplished. The models help us find the optimal software system structure while considering basic information on reliability and cost of modules. Each model is applicable to a distinct situation. All four models maximize reliability while ensuring that expenditures remain within budget.

Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.

Cys-loop receptor neurotransmitter-gated ion channels are pentameric assemblies of subunits that contain three domains: extracellular, transmembrane, and intracellular. The extracellular domain forms the agonist binding site. The transmembrane domain forms the ion channel. The cytoplasmic domain is involved in trafficking, localization, and modulation by cytoplasmic second messenger systems but its role in channel assembly and function is poorly understood and little is known about its structure. The intracellular domain is formed by the large (>100 residues) loop between the α-helical M3 and M4 transmembrane segments. Putative prokaryotic Cys-loop homologues lack a large M3M4 loop. We replaced the complete M3M4 loop (115 amino acids) in the 5-hydroxytryptamine type 3A (5-HT3A) subunit with a heptapeptide from the prokaryotic homologue fromGloeobacter violaceus. The macroscopic electrophysiological and pharmacological characteristics of the homomeric 5-HT3A-glvM3M4 receptors were...

Background: Since the full genome sequences of Saccharomyces cerevisiae were released in 1996, genome sequences of over 90 fungal species have become publicly available. The heterogeneous formats of genome sequences archived in different sequencing centers hampered the integration of the data for efficient and comprehensive comparative analyses. The Comparative Fungal Genomics Platform (CFGP) was developed to archive these data via a single standardized format that can support multifaceted and integrated analyses of the data. To facilitate efficient data visualization and utilization within and across species based on the architecture of CFGP and associated databases, a new genome browser was needed.

Most ligands targeting RNA are identified through screening a therapeutic target for binding members of a ligand library. A potential alternative way to construct RNA binders is through rational design using information about the RNA motifs ligands prefer to bind. Herein, we describe such an approach to design modularly assembled ligands targeting the RNA that causes myotonic dystrophy type 2 (DM2), a currently untreatable disease. A previous study identified that 6′-N-5-hexynoate kanamycin A (1) prefers to bind 2×2 nucleotide, pyrimidine-rich RNA internal loops. Multiple copies of such loops were found in the RNA hairpin that causes DM2. The 1 ligand was then modularly displayed on a peptoid scaffold with varied number and spacing to target several internal loops simultaneously. Modularly assembled ligands were tested for binding to a series of RNAs and for inhibiting the formation of the toxic DM2 RNA-muscleblind protein (MBNL-1) interaction. The most potent ligand displays three 1 modules, each separated by four spacing submonomers, and inhibits the formation of the RNA-protein complex with an IC 50 of 25 nM. This ligand is higher affinity and more specific for binding DM2 RNA than MBNL-1. It binds the DM2 RNA at least 20times more tightly than related RNAs and 15-fold more tightly than MBNL-1. A related control peptoid displaying 6′-N-5-hexynoate neamine (2) is >100-fold less potent at inhibiting the RNAprotein interaction and binds to DM2 RNA >125-fold more weakly. Uptake studies into a mouse myoblast cell line also show that the most potent ligand is cell permeable.

In this paper, we develop a theory of modular design and refinement of hierarchical hybrid systems. In particular, we present compositional trace-based semantics for the language Charon that allows modular specification of interacting hybrid systems. For hierarchical description of the system architecture, Charon supports building complex agents via the operations of instantiation, hiding, and parallel composition. For hierarchical description of the behavior of atomic components, Charon supports building complex modes via the operations of instantiation, scoping, and encapsulation. We develop an observational trace semantics for agents as well as for modes, and define a notion of refinement for both, based on trace inclusion. We show this semantics to be compositional with respect to the constructs in the language.

The development of complex mechatronic systems requires a careful and ideally verifiable design. In addition, engineers from different disciplines, namely mechanical, electrical and software engineering, have to cooperate. The current technology is to use block diagrams including discrete blocks with statecharts for the design and verification of such systems. This does not adequately support the verification of large systems which improve the system behavior at run-time by means of online reconfiguration of its controllers because the system as whole has to be verified. It also does not support cooperative interdisciplinary work because a white-box view on all blocks involved in the online reconfiguration is required. This paper proposes a rigorous component concept based on the notion of UML component diagrams which enables modular composition and decomposition of complex systems with online reconfiguration given by hierarchical hybrid component specifications. The approach enable...

OpenTracker, an open software architecture that provides a generic solution to the different tasks involved in tracking input devices and processing tracking data for virtual environments. It combines a highly modular design with a configuration syntax based on XML, thus taking full advantage of this new technology. OpenTracker is a first attempt towards a "write once, track anywhere" approach to virtual reality application development. To support these claims, integration into an existing augmented reality system is demonstrated. Once development is sufficiently mature, it is planned to make Open-Tracker available to the public under an open source software license. ¢ An object-oriented approach to an extensive set of sensor access, filtering, fusion, and state transformation operations ¢ Behavior specification by constructing graphs of tracking objects (similar in spirit to scene graphs or event cascades) from user defined tracker configuration files ¢ Distributed simulation by network transfer of tracker state at any point in the graph structure ¢ Decoupled simulation by transparent multi-threading and networking ¢ A software engineering approach based on XML [6], which allows to use many generic tools such as 9, for development, documentation, and configuration.

The logic gates NAND/NOR were mimicked by enzyme biocatalyzed reactions activated by sucrose, maltose and phosphate. The subunits performing AND/OR Boolean logic operations were designed using maltose phosphorylase and cooperative work of invertase/amyloglucosidase, respectively. Glucose produced as the output signal from the AND/OR subunits was applied as the input signal for the INVERTER gate composed of alcohol dehydrogenase, glucose oxidase, microperoxidase-11, ethanol and NAD + , which generated the final output in the form of NADH inverting the logic signal from 0 to 1 or from 1 to 0. The final output signal was amplified by a self-promoting biocatalytic system. In order to fulfill the Boolean properties of associativity and commutativity in logic networks, the final NADH output signal was converted to the initial signals of maltose and phosphate, thus allowing assembling of the same standard units in concatenated sequences. The designed modular approach, signal amplification and conversion processes open the way toward complex logic networks composed of standard elements resembling electronic integrated circuitries.

This paper develops a modularization scheme based on the functional model of a system. The modularization approach makes use of the function-behavior-state (FBS) model of the system to derive the entity relations. The design structure matrix (DSM) is automatically constructed based on the FBS model. In this way, the tedious work of filling the DSM entries based on expert knowledge is avoided. The approach makes use of k-means clustering algorithm to allow the user to try different number of clusters in a fast way. The k-means clustering is adopted for DSM based modularization by defining a proper entity representation, relation measure and objective function. Two modularization schemes are performed, one based on the immediate relations and one on the deeper behavioral relations between the components. Considering the application on the shifting system of the Delft University of Technology (DUT) Formula Student car, the latter modularization resulted in more mechatronic behavior based modules, while the former resulted in modules based on mere disciplinary and spatial closeness.

We present a software module which allows one to efficiently perform molecular dynamics and local minimization calculations in internal coordinates when incorporated into a molecular dynamics package. We have implemented a reference interface to the NIH version of the X-PLOR structure refinement package and show that the module provides superior torsion angle dynamics functionality relative to the native X-PLOR implementation. The module has been designed in a portable fashion so that interfacing it with other packages should be relatively easy. Other features of the module include the ability to define rather general internal coordinates, an accurate integration algorithm which can automatically adjust the integration step size, and a modular design which facilitates extending and enhancing the module.

Abstmct-In this paper, we present a systematic method of implementing a VLSI parallel adder. First, we define a family of adders, based on a modular design. Our design uses three types of component cells, which we implement in static CMOS. We then formulate the adder design as a dynamic programming problem, optimizing with respect to area and time. The result is an area-time optimal adder in our design family. We illustrate our approach by implementing a 66-bit adder for use in a floating point processor. In addition, we indicate how to use our method for implementations in technologies and design styles other than static CMOS.